Equine Polysaccharide Storage Myopathy

Equine polysaccharide storage myopathy (EPSM) is a sub-type of exertional rhabdomyolysis characterized by a defect in glycogen storage in skeletal muscle.  This disease is seen in many different breeds including Quarter horses, draft horses and crosses of these breeds.  There is evidence that the disease is heritable in Quarter horses; this question has not been answered for other breeds.  Skeletal muscles in affected horses have higher amounts of stored glycogen than in normal horses.  Affected horses also have higher levels of a complex polysaccharide which is resistant to amylase digestion, aiding identification of the disease by histopathology as described below.

  Clinical signs of EPSM are similar to those of all forms of rhabdomyolysis:  stiff gait, pain, muscle cramping, and reluctance to move after exercise.  However, in some subclinically affected horses, EPSM is not discovered until unusual events (such as anesthesia and subsequent postanesthetic recumbency) occur.  A diagnosis of rhabdomyolysis can be made from clinical signs and serum chemistry values.  Muscle enzymes such as creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate transminase (AST) will be high after episodes of rhabdomyolysis.  Furthermore, diagnosis of rhabdomyolysis does not specify the underlying metabolic problem.  In humans and other species there are numerous metabolic disturbances in glycogenolysis or glycolysis that cause rhabdomyolysis.  To date, however, the specific etiology of EPSM has not been elucidated.  Studies have shown that EPSM is not a defect in glycogenolysis or glycolysis.  Instead, it is believed to be due to increased glucose uptake, possibly due to up-regulation of insulin receptors because affected horses have an exaggerated response to insulin.

  EPSM must be differentiated from equine motor neuron disease (EMND), colic, equine protozoal myeloencephalitis (EPM), musculoskeletal injury, hyperkalemic periodic paralysis (HYPP) and even Lyme disease.  EMND is an idiopathic degenerative disease of somatic nerves originating in the ventral horn of the spinal cord.  These horses will show weakness and trembling due to neurogenic atrophy of type 1, versus type 2 in EPSM, muscle fibers which make up the postural muscles.  EPSM can mimic colic because affected horses show signs of discomfort; however, a thorough examination of the gastrointestinal tract will rule out colic.  Horses with EPM will often have asymmetrical atrophy.  The stiff gait of horses with EPSM may mimic the proprioceptive deficits associated with EPM, but a thorough neurological exam will reveal that horses with EPSM do not cross their pelvic limbs on tight turns.  EPSM can look like musculoskeletal injury, as a crouched gait can be a sign of back injury.  Stiff gate with decreased flexion is common in both disorders.  A thorough physical examination, radiographs, and nuclear scintigraphy should determine if the horse actually has a musculoskeletal disorder.  As there is a familial basis in Quarter horses for both EPSM and HYPP, the two must be differentiated. HYPP DNA testing can be done by submitting a blood sample to Veterinary Genetics Laboratory (phone 916.752.7416 for instructions.)

(see addendum for additional information)

Finally, Lyme disease can manifest as shifting leg lameness, stiffness and discomfort.  Polymerase chain reaction of synovial fluid of affected horses will reveal infection with Borrelia burgdorferi if the horse is infected with Lyme disease.  If the above diseases and syndromes cannot be differentiated, a muscle biopsy can be done.

  EPSM and EMND are best differentiated by muscle biopsy.  The epaxial muscles, specifically the sacrocaudalis dorsalis medialis, are made of type 1 fibers and are good samples for EMND diagnosis.  For diagnosis of EPSM, a biopsy of the semitendinosus muscle is a good choice as this is a type 2 muscle, therefore locomotory, and is affected in EPSM.  To obtain the best biopsy sample, the horse should be sedated and administered local anesthesia with either a caudal epidural or line block over the incision site, without actually injecting into the muscle to be sampled.  Make a 5 cm longitudinal skin incision parallel to the muscle fibers.  Repeat through the fascia.  Obtain a strip of muscle approximately 5 cm in length by 1 cm in diameter.  Be sure to undermine the muscle first so it does not retract when one end is cut.  Place the tissue sample in 10% formalin and submit for histopathologic examination.  Punch biopsies do not provide enough tissue for evaluation of EPSM or EMND.

  The best tissue stain to identify EMND is Masson's trichrome.  EPSM is identified best by staining with both PAS and PAS with amylase digestion.  In both EMND and EPSM, there will be excessive variation in muscle fiber size, internal nuclei, and hypertrophy.  If the horse has EMND, the muscle cells will have fibrosis and fat infiltration, scattered necrotic and regenerative areas, and intramuscular nerves will be atrophied.  In the case of EPSM, the muscle cells will have vacuoles, small rounded fibers, normal intramuscular nerves and glycogen/polysaccharide granules which will not be digested by amylase.

  Treatment for EPSM, once diagnosis is made, is primarily dietary therapy.  In the past, standard therapy for horses with rhabdomyolysis has been to remove excess carbohydrate, often in the form of grain, from the diet.  In the case of EPSM, this is not enough as the horse still makes too much abnormal polysaccharide.  Replacement of carbohydrates with a diet high in fat (up to 25%) and protein has worked well to control signs of EPSM by forcing the horse to metabolize fat and protein for energy.  Within six months, many horses treated with this diet resumed training to previous levels, without signs of EPSM and without elevated CK, LDH or AST.  Furthermore, horses benefited most from as little rest as possible and recovered sooner than horses treated only with diet modification.

  Horses with EPSM often have abnormal thyroid hormone levels despite normally functioning thyroid glands ("euthyroid sick syndrome"); therefore thyroid supplements do not help.  Interestingly, horses on the high fat diet resolved their thyroid and vitamin E/ selenium imbalances.  This is likely due to better muscle function with fat as an energy source.  Once diagnosed, EPSM is treatable; the animal has a reasonable prognosis for return to work.  However, because EPSM may be inherited, the veterinarian should advise clients against breeding affected horses.

- by Catherine Alinovi, Class of 2001

- edited by Karen Tucker-Gillum, DVM,

    ADDL Graduate Student

Addendum

An helpful reader pointed out on 5/7/02 that this information needs to be changed:

"The UC Davis Veterinary Laboratory no longer accepts blood
samples for HYPP testing. They only want mane or tail hair that has been
pulled-it needs the root hooks. 20-30 hairs put into a paper envelope and a
separate sample submission form- The phone number for the HYPP desk is
530-752-9780-.... The main line is 530-752-2211 for any other
type questions."